Stroke is the fifth leading cause of death and the primary cause of preventable disability in the U.S according to the most recent statistics by the American Heart Association (Mozaffarian et al. 2016). Each year, approximately 795,000 people continue to experience a new or recurrent stroke. On average, every 40 seconds, someone in the United States has a stroke, and someone dies of one approximately every 4 minutes. Identification of patients with high-risk, asymptomatic carotid plaques remains thus an elusive but essential step in stroke prevention. One such criterion is plaque stiffness. Lipid plaques have been shown to have distinct stiffness from calcified plaques. Increased arterial stiffness has also been reported in stroke patients. However, none of the medical imaging modalities in the clinic can provide such information. Current criteria thus relate to the vessel lumen properties but not directly to the carotid wall itself that bears the plaque, confirming the challenge at hand. A criterion that would reliably identify unstable plaques would ensure timely removal through carotid endarterectomy (CEA), especially in asymptomatic patients or those with low endoluminal stenosis whose stroke risk is currently poorly assessed. To that end, our group has pioneered the noninvasive, ultrasound- based technique of Pulse Wave Imaging (PWI) that depicts the intrinsic pulse wave propagation along the vessel wall and maps the underlying pulse-wave induced wall displacement and compliance using high-frame-rate, high-precision motion estimation seamlessly integrated with the corresponding sonogram. PWI has been shown capable of characterizing plaques based on their distinct underlying stiffness In this study, we aim at the characterization of carotid plaques for timely prognosis of ischemic stroke. We hypothesize that PWI can significantly reinforce the prognostic capability of a conventional vascular ultrasound. The team assembled is highly multi- disciplinary encompassing all research fields such as ultrasound, biomechanics, clinical radiology, vascular pathology, vascular surgery and biostatistics. The specific aims are thus to: 1) Optimize and assess fundamental performance of PWI in experimental phantoms; 2) Assess capability of PWI to characterize plaque stiffness in pigs in vivo; 3) Validate PWI findings in carotid plaques of patients in vivo. Following the proposed optimization and validation studies, this highly translational technology could be readily integrated in clinical ultrasound scanners for carotid plaque stability assessment and stroke prevention. PWI can be used in conjunction with a standard vascular ultrasound scan and the compliance map can be overlaid onto a standard B-mode to identify the plaque mechanical properties and thus overall stability.